Neural Correlates of Recognition Memory in Children with Febrile Seizures: Evidence from Functional Magnetic Resonance Imaging

Febrile seizures (FS) are assumed to not have adverse long-term effects on cognitive development. Nevertheless, FS are often associated with hippocampal sclerosis which can imply episodic memory deficits. This interrelation has hardly been studied so far. In the current study 13 children who had suffered from FS during infancy and 14 control children (7 to 9-years-old) were examined for episodic and semantic memory with standardized neuropsychological tests. Furthermore, using functional magnetic resonance imaging (fMRI) we studied neuronal activation while the children performed a continuous recognition memory task. The analysis of the behavioral data of the neuropsychological tests and the recognition memory experiment did not reveal any between-group differences in memory performance. Consistent with other studies fMRI revealed repetition enhancement effects for both groups in a variety of brain regions (e.g., right middle frontal gyrus, left parahippocampal gyrus) and a repetition suppression effect in the right superior temporal gyrus. Different neural activation patterns between both groups were obtained selectively within the right supramarginal gyrus (BA 40). In the control group correct rejections of new items were associated with stronger activation than correctly identified old items (HITs) whereas in the FS group no difference occurred. On the background that the right supramarginal gyrus is assumed to mediate a top-down process to internally direct attention toward recollected information, the results could indicate that control children used strategic recollection in order to reject new items (recall-to-reject). In contrast, the missing effect in the FS group could reflect a lack of strategy use, possibly due to impaired recollective processing. This study demonstrates that FS, even with mainly benign courses, can be accompanied by selective modifications in the neural structures underlying recognition memory

Histamine can be Formed and Degraded in the Human and Mouse Heart

Histamine is metabolized by several enzymes in vitro and in vivo. The relevance of this metabolism in the mammalian heart in vivo is unclear. However, histamine can exert positive inotropic effects (PIE) and positive chronotropic effects (PCE) in humans via H2- histamine receptors. In transgenic mice (H2-TG) that overexpress the human H2 receptor in cardiomyocytes but not in wild-type littermate mice (WT), histamine induced PIE and PCE in isolated left or right atrial preparations. These H2-TG were used to investigate the putative relevance of histamine degrading enzymes in the mammalian heart. Histidine, the precursor of histamine, increased force of contraction (FOC) in human atrial preparations. Moreover, histamine increased the phosphorylation state of phospholamban in human atrium. Here, we could detect histidine decarboxylase (HDC) and histamine itself in cardiomyocytes of mouse hearts. Moreover, our data indicate that histamine is subject to degradation in the mammalian heart. Inhibition of the histamine metabolizing enzymes diamine oxidase (DAO) and monoamine oxidase (MAO) shifted the concentration response curves for the PIE in H2-TG atria to the left. Moreover, activity of histamine metabolizing enzymes was present in mouse cardiac samples as well as in human atrial samples. Thus, drugs used for other indication (e.g. antidepressants) can alter histamine levels in the heart. Our results deepen our understanding of the physiological role of histamine in the mouse and human heart. Our findings might be clinically relevant because we show enzyme targets for drugs to modify the beating rate and force of the human heart

Patent Retrieval in Chemistry based on semantically tagged Named Entities

Gurulingappa H, Müller B, Klinger R, et al. Patent Retrieval in Chemistry based on semantically tagged Named Entities. In: Voorhees EM, Buckland LP, eds. The Eighteenth Text RETrieval Conference (TREC 2009) Proceedings. Gaithersburg, Maryland, USA; 2009.This paper reports on the work that has been conducted by Fraunhofer SCAI for Trec Chemistry (Trec-Chem) track 2009. The team of Fraunhofer SCAI participated in two tasks, namely Technology Survey and Prior Art Search. The core of the framework is an index of 1.2 million chemical patents provided as a data set by Trec. For the technology survey, three runs were submitted based on semantic dictionaries and noun phrases. For the prior art search task, several elds were introduced into the index that contained normalized noun phrases, biomedical as well as chemical entities. Altogether, 36 runs were submitted for this task that were based on automatic querying with tokens, noun phrases and entities along with dierent search strategies

Serological responses to koi herpesvirus (KHV) in a non-cyprinid reservoir host

Koi herpesvirus (KHV) is a highly contagious virus that causes KHV disease (KHVD) inducing high mortality in carp and koi (Cyprinus carpio L.). In the late stage, latency occurs with very low, often non-detectable virus concentrations, which represents a challenge for virus detection. After validation according to OIE recommendations, an antibody ELISA was established to recognize antibodies of C. carpio against KHV infection. In this study, the ELISA was modified to detect anti-KHV antibodies from a non-cyprinid fish. Experimentally infected rainbow trout (Oncorhynchus mykiss) were able to transmit KHV to naïve carp at two different temperatures, demonstrating their potential as a reservoir host. At 20°C, KHVD was induced in carp but not at 15°C. Unexpectedly, rainbow trout developed humoral response against KHV at both temperatures. In contrast to carp, at 15°C trout produced neutralizing antibodies but not at 20°C. While antibodies obtained from infected carp sera reacted in a similar way against all KHV, antibodies from rainbow trout sera reacted differently to the same isolates by ELISA. The data show that even when non-cyprinid fish species are infected with KHV, they can produce antibodies that differ from those observed in carp

The programme on ecosystem change and society (PECS)–a decade of deepening social-ecological research through a place-based focus

The Programme on Ecosystem Change and Society (PECS) was established in 2011, and is now one of the major international social-ecological systems (SES) research networks. During this time, SES research has undergone a phase of rapid growth and has grown into an influential branch of sustainability science. In this Perspective, we argue that SES research has also deepened over the past decade, and helped to shed light on key dimensions of SES dynamics (e.g. system feedbacks, aspects of system design, goals and paradigms) that can lead to tangible action for solving the major sustainability challenges of our time. We suggest four ways in which the growth of place-based SES research, fostered by networks such as PECS, has contributed to these developments, namely by: 1) shedding light on transformational change, 2) revealing the social dynamics shaping SES, 3) bringing together diverse types of knowledge, and 4) encouraging reflexive researchers

The 20S Proteasome Splicing Activity Discovered by SpliceMet

The identification of proteasome-generated spliced peptides (PSP) revealed a new unpredicted activity of the major cellular protease. However, so far characterization of PSP was entirely dependent on the availability of patient-derived cytotoxic CD8+ T lymphocytes (CTL) thus preventing a systematic investigation of proteasome-catalyzed peptide splicing (PCPS). For an unrestricted PSP identification we here developed SpliceMet, combining the computer-based algorithm ProteaJ with in vitro proteasomal degradation assays and mass spectrometry. By applying SpliceMet for the analysis of proteasomal processing products of four different substrate polypeptides, derived from human tumor as well as viral antigens, we identified fifteen new spliced peptides generated by PCPS either by cis or from two separate substrate molecules, i.e., by trans splicing. Our data suggest that 20S proteasomes represent a molecular machine that, due to its catalytic and structural properties, facilitates the generation of spliced peptides, thereby providing a pool of qualitatively new peptides from which functionally relevant products may be selected

Novel insights into the mechanisms mediating the local antihypertrophic effects of cardiac atrial natriuretic peptide: role of cGMP-dependent protein kinase and RGS2

Cardiac atrial natriuretic peptide (ANP) locally counteracts cardiac hypertrophy via the guanylyl cyclase-A (GC-A) receptor and cGMP production, but the downstream signalling pathways are unknown. Here, we examined the influence of ANP on β-adrenergic versus Angiotensin II (Ang II)-dependent (Gs vs. Gαq mediated) modulation of Ca2+i-handling in cardiomyocytes and of hypertrophy in intact hearts. L-type Ca2+ currents and Ca2+i transients in adult isolated murine ventricular myocytes were studied by voltage-clamp recordings and fluorescence microscopy. ANP suppressed Ang II-stimulated Ca2+ currents and transients, but had no effect on isoproterenol stimulation. Ang II suppression by ANP was abolished in cardiomyocytes of mice deficient in GC-A, in cyclic GMP-dependent protein kinase I (PKG I) or in the regulator of G protein signalling (RGS) 2, a target of PKG I. Cardiac hypertrophy in response to exogenous Ang II was significantly exacerbated in mice with conditional, cardiomyocyte-restricted GC-A deletion (CM GC-A KO). This was concomitant to increased activation of the Ca2+/calmodulin-dependent prohypertrophic signal transducer CaMKII. In contrast, β-adrenoreceptor-induced hypertrophy was not enhanced in CM GC-A KO mice. Lastly, while the stimulatory effects of Ang II on Ca2+-handling were absent in myocytes of mice deficient in TRPC3/TRPC6, the effects of isoproterenol were unchanged. Our data demonstrate a direct myocardial role for ANP/GC-A/cGMP to antagonize the Ca2+i-dependent hypertrophic growth response to Ang II, but not to β-adrenergic stimulation. The selectivity of this interaction is determined by PKG I and RGS2-dependent modulation of Ang II/AT1 signalling. Furthermore, they strengthen published observations in neonatal cardiomyocytes showing that TRPC3/TRPC6 channels are essential for Ang II, but not for β-adrenergic Ca2+i-stimulation in adult myocytes

The programme on ecosystem change and society (PECS) – a decade of deepening social-ecological research through a place-based focus

The Programme on Ecosystem Change and Society (PECS) was established in 2011, and is now one of the major international social-ecological systems (SES) research networks. During this time, SES research has undergone a phase of rapid growth and has grown into an influential branch of sustainability science. In this Perspective, we argue that SES research has also deepened over the past decade, and helped to shed light on key dimensions of SES dynamics (e.g. system feedbacks, aspects of system design, goals and paradigms) that can lead to tangible action for solving the major sustainability challenges of our time. We suggest four ways in which the growth of place-based SES research, fostered by networks such as PECS, has contributed to these developments, namely by: 1) shedding light on transformational change, 2) revealing the social dynamics shaping SES, 3) bringing together diverse types of knowledge, and 4) encouraging reflexive researchers

Concurrence of rule-and similarity-based mechanisms in artificial grammar learning

A current theoretical debate regards whether rule-based or similarity based learning prevails during artificial grammar learning (AGL). Although the majority of findings are consistent with a similarity based account of AGL it has been argued that these results were obtained only after limited exposure to study exemplars, and performance on subsequent grammaticality judgment tests has often been barely above chance level. In three experiments the conditions were investigated under which rule-and similarity based learning could be applied. Participants were exposed to exemplars of an artificial grammar under different (implicit and explicit) learning instructions. The analysis of receiver operating characteristics (ROC) during a final grammaticality judgment test revealed that explicit but not implicit learning led to rule knowledge. It also demonstrated that this knowledge base is built up gradually while similarity knowledge governed the initial state of learning. Together these results indicate that rule-and similarity-based mechanisms concur during AGL. Moreover, it could be speculated that two different rule processes might operate in parallel ; bottom-up learning via gradual rule extraction and top-down learning via rule testing. Crucially, the latter is facilitated by performance feedback that encourages explicit hypothesis testing

Age of acquisition modulates neural activity for both regular and irregular syntactic functions

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